Sterilization and decontamination of sealable enclosures and their contents has become equally as important today as the sterilization of products and devices. A number of chapters in Aseptic Pharmaceutical Manufacturing II discuss the use of barriers technology in the pharmaceutical industry and the need to decontaminate the interior of the barriers (sealable enclosures). The closed-loop flow-through decontamination systems disclosed in U.S. Pat. No. 5,173,258, U.S. Pat. No. 5,876,664, and U.S. Pat. No. 5,906,794, incorporated by reference herein, are useful for delivering sterilant vapors to sealable enclosures such as glove boxes, biological safety cabinets, the isolators used for sterility testing of pharmaceutical products, pharmaceutical form-fill-seal lines and small clean rooms. The open-loop flow-through decontamination system disclosed in U.S. Pat. No. 4,909,999, incorporated by reference herein, was intended for use with water-jacketed CO2 incubators but could also be used with other sealable enclosures. More recent applications include decontamination of buildings such as post offices U.S. Ser. No. 24/184,950 and decontamination of aircraft U.S. Ser. No. 25/074,359, both incorporated herein by reference.
Improvements are being made continuously in the methods and systems that are used to accomplish flow through sterilization as evidenced by the patents that have been filed in recent years. U.S. Pat. No. 5,445,792 and U.S. Pat. No. 5,508,009, both incorporated by reference herein, disclose a method of maintaining a pre-determined percent saturation by adjusting the rate of hydrogen peroxide injection in response to a predetermined characteristic of the carrier gas. U.S. Pat. No. 5,876,664 and U.S. Pat. No. 5,906,794 disclose a method of controlling both percent saturation and sterilant vapor concentration. U.S. Pat. No. 5,872,359, incorporated by reference herein, discloses a real-time monitor and control system that controls both percent saturation and sterilant vapor concentration.
Sensors that can measure the concentration of the sterilant vapor, typically hydrogen peroxide, in the presence of water vapor are the subjects of a number of issued patents and pending applications including U.S. Ser. No. 56/000,142, U.S. Pat. No. 5,608,156, U.S. Pat. No. 5,847,392, U.S. Pat. No. 5,847,393, U.S. Pat. No. 6,189,368, U.S. Pat. No. 6,269,680, U.S. Pat. No. 6,517,775, U.S. Pat. No. 6,532,794, U.S. Pat. No. 6,537,491, U.S. Pat. No. 6,875,399, U.S. Ser. No. 22/168,289, U.S. Ser. No. 23/021,724, and U.S. Ser. No. 23/115,933, all incorporated herein by reference. Methods to calibrate the sterilant vapor sensors are the subjects of a number of issued patents and pending applications including U.S. Pat. No. 6,581,435, U.S. Pat. No. 6,612,149, U.S. Pat. No. 6,742,378, U.S. Ser. No. 22/152,792, and U.S. Ser. No. 24/016,283, all incorporated herein by reference.
U.S. Pat. No. 5,173,258 discloses the closed loop flow-through system that was commercialized in the highly successful Steris VHP®11000 bio-decontamination system. This system preconditions the air in a sealable enclosure by re-circulating the air through an air dryer until it is at, or below, a pre-determined humidity level. If the air initially has little to no humidity no pre-conditioning is necessary. The air continues to circulate in a closed loop during the decontamination process with vaporized sterilant continuously being generated and mixed with the dehumidified air as it flows into the enclosure. As the partially degraded sterilant and air returns from the enclosure, it passes through a catalytic converter and an air dryer before being heated and combined with vaporized sterilant and returned to the enclosure. The continuous removal of partially degraded sterilant and replacement with freshly generated sterilant maximizes the concentration of the sterilant vapor within the enclosure. However, as the enclosure size increases and the air exchange rate begins to decrease, the system cannot maintain both the vapor concentration and the percent saturation for an extended period of time. FIGS. 5, 6 and 7 in U.S. Pat. No. 5,173,258 illustrate how the allowable concentration decreases with time for lower air exchange rates. FIG. 3 in U.S. Pat. No. 5,906,794 shows how the percent saturation increases with time during a decontamination cycle and can exceed dew point conditions resulting in condensation and a loss of kill efficacy.
The moisture content of the air exiting the air dryer will depend upon the humidity of the air when it enters the air dryer, the air flow rate, the temperature of the air dryer and the remaining capacity of the air dryer. In general, the moisture content of the exit air will increase over time. A steady state for both sterilant vapor concentration and percent saturation cannot be maintained if the rate at which humidity is being removed from the enclosure is not equal to the rate at which water vapor is being introduced into the enclosure. A combination of sterilant vapor sensors, humidity sensors, airflow sensors and temperature sensors used in combination with complex control algorithms cannot control both sterilant vapor concentration and percent saturation for low air exchange rates when the liquid form of the sterilant contains both water and the sterilant because they cannot be introduced independently. Control is further complicated if the sterilant (eg: hydrogen peroxide vapor) degrades into multiple components, one of which is water, during the decontamination process. The best the system can do is to maintain the system at 100% saturation. The combined in-accuracies of the sensors will determine the degree to which the sterilant concentration is monitored and to which the percent saturation is controlled. Redundant, independent sensors may be used in some applications if the failure of a sensor would result in an unacceptable outcome.
The system disclosed in U.S. Pat. No. 5,173,258 requires regeneration when the desiccant capacity has been depleted. The regeneration process is described starting at line 34 in column 8. Regeneration is accomplished by blowing hot air through the desiccant bed to remove the moisture from the bed and discharge it to an outside exhaust. US 2003/0164091 discloses a replaceable desiccant cartridge that could either be discarded after use, or regenerated after use. The cartridge could be removed and regenerated elsewhere as disclosed in the patent application, or an automated switching system could be devised to use one cartridge while another is being regenerated. The system disclosed in U.S. Pat. No. 5,906,794 also uses a desiccant that requires regeneration. A bypass of the air dryer is provided so that the air stream humidity can be controlled to some level that is higher than the output of the air dryer by controlling the amount of air that bypasses the air dryer. A continuously regenerating desiccant wheel could be used with this system as it has a blower on each side of the air dryer. The pressure in the drying portion of the desiccant wheel could be controlled relative to the pressure in the regenerating portion of the wheel minimizing leakage from one side to the other.
All three of the systems mentioned thus far should be able to generate output air streams with humidity levels at, or below, about 30% RH at 25° C. A batch mode system may generate an output air stream with a lower humidity level; however, a continuously operating desiccant system will not be able to do so because the desiccant bed temperature is elevated from the continuous regeneration. The output humidity of the batch mode system will vary over time as the desiccant bed heats up as it absorbs moisture and as the capacity of the bed to remove moisture is depleted. This would present a problem if the batch mode system were to be used as a source of hydrogen peroxide vapor in a steady state environment such as that disclosed in U.S. Pat. No. 5,114,670; U.S. Pat. No. 6,752,959; U.S. Pat. No. 4,742,667 and U.S. Pat. No. 6,752,959; all incorporated herein by reference. The method of the present invention would be able to supply the vapor continuously, at the same vapor concentration level and at the same percent saturation level, and would work well in these applications.
Great Briton patent GB 2308066A, incorporated herein by reference, discloses a dehumidification method beginning with line 7 on page 13 that utilizes a refridgerative air dryer consisting of three heat exchangers. The first heat exchanger cools the air down to around 10° C. The second and third heat exchangers are in parallel. While one is cooled to below freezing and “on line”, the other is warmed and “off line”. Water is taken out of the air stream as ice by the cold heat exchanger while the “off line” heat exchanger is defrosting. The level of dehumidification is not easy to control with this system as ice is building up on the “on-line” heat exchanger during normal operation and this changes the dynamics of the airflow and the transfer of heat from the air stream.
Table 1 lists the saturation concentration of water vapor for temperatures up to 30° C. The saturation concentration for water vapor at about 5° C. (6.795 mg/liter) is approximately equal to the water vapor content at 30% RH and 25° C. (0.3*23.046=6.91 mg/liter) of the “dry air” produced by the desiccant drying systems. This would suggest that bubbling air through a water bath that is at about 5° C. would produce a stream of air with a humidity that is similar to that exiting the air dryer.
TABLE 1Water vapor Saturation at Various Temperatures up to 30° C.TEMPH20 SAT.TEMPH20 SAT.TEMPH20 SAT.° C.mg/l° C.mg/l° C.mg/l04.847312109.3958632017.289710.5555565.03628510.555569.73261620.5555617.860311.1111115.2316911.1111110.0798621.1111118.448591.6666675.43363911.6666710.4378121.6666719.051992.2222225.64244912.2222210.8060722.2222219.6722.7777785.85829212.7777811.1863922.7777820.307953.3333336.08136113.3333311.577723.3333320.964423.8888896.31162813.8888911.9812423.8888921.638414.4444446.54955914.4444412.3966224.4444422.3291256.7954491512.824362523.042165.5555567.04933715.5555613.2650825.5555623.773996.1111117.31123316.1111113.7195226.1111124.523756.6666677.5818416.6666714.1860726.6666725.294357.2222227.86127117.2222214.6679927.2222226.085197.7777788.14921517.7777815.1622527.7777826.899948.3333338.44656618.3333315.6725528.3333327.733578.8888898.75350418.8888916.1970828.8888928.589899.4444449.06970519.4444416.7351829.4444429.4682109.3958632017.289713030.36761
Chilling the water bath to as low as 0° C. should produce a stream of air with an absolute humidity near 4.84 mg/liter which is equivalent to 21% RH at 25° C. (=100*4.84/23.04216). The humidity of the air stream is automatically decreased, or increased, so that it exits at saturation when it passes through the cold water bath. The desiccant air dryers and the refridgerative air dryers disclosed in the prior art can only reduce the humidity of the air stream. They do not increase it when the air is initially dry. The air dryer bypass 36 in FIG. 6 of U.S. Pat. No. 5,906,794 will also not increase the humidity of the air stream if it is initially dry. Humidity would have to be introduced into the air stream by another method.
Chilling water to 0° C. and maintaining it at 0° C. is fairly easy to do. One calorie of energy is required to reduce the temperature of one gram of water one degree Centigrade. An additional 79.7 calories are required to freeze the water and start to drop the temperature further. Thus, one only needs to cool the water until the temperature stops dropping and it will be at the freezing point.
Assume a continuous recirculating system with a 20 SCFM airflow and a post water bath temperature of 32° F. The recirculating air stream is heated and 6.63 grams per minute of water is vaporized into the air stream resulting in a 95° F. temperature of the moist air stream. The moist air stream flows through a sealed enclosure and back into the water bath where it is cools to 32° F. condensing the entire 6.63 grams per minute of water vapor. The absolute humidity of the 100% saturated air at 32° F. is about 0.1373 grams per cubic foot. The thermal energy required to keep this system operating continuously is estimated in Table 2:
TABLE 2Energy RequirementsStep requiring EnergyEnergy CalculationEnergyHeat 20 SCFM of air from 32° F. to 86° F.20 * (86-32) * 0.0771 * 0.2419.98 btu/minHeat 0.1373 grams water vapor/ft3 32° F.20 * (86-32) * 0.1373 * 1/454 0.33 btu/minto 86° F.Vaporize 6.63 grams per minute of water6.63/454 * 105515.41 btu/minCool 20 SCFM of air from 86° F. to 32° F.20 * (86-32) * 0.0771 * 0.2419.98 btu/minCool 0.1373 gram/ft3 from 86° F. to 32° F.20 * (86-32) * 0.1373 * 1/454 0.33 btu/minCondense 6.63 grams per minute of water6.63/454 * 105515.41 btu/minTotal Energy71.44 btu/min = 1.26 KW
When a refrigeration system is used to cool the water bath, the recirculating air stream can be passed over the condenser coils generating all of the energy required to heat the air from 32° F. to 86° F. reducing the thermal energy requirements to about 0.9 KW. If the air blower is placed downstream of the water bath, the heat generated by the blower will elevate the air temperature further reducing the energy required during the liquid decontaminant injection and vaporization that follows. The Ametek Lamb Infin-A-Tek Model 121001-13 two-stage, peripheral discharge blower specifications are contained in Table 3. About four hundred watts of thermal energy are typically generated and absorbed by the air stream when the blower is operating against a vacuum head ranging from 36 to 80 inches of water column.
TABLE 3Ametek Lamb Infin-A-Tek Model 121001-13 Blower PerformanceOrificeVacFlowAir(Inches)AmpsWattsRPM(In.H2O)(CFM)Watts213.71454226405.6123.6811.7513.71453225509.3121.31331.51414802247015.4113.12051.2514.1154322430271043301.12514.115382235035.696.4404114.115382235045.8864630.87513.915252250057.173.44930.7513.514362278067.858.54670.62512.913582338078.643.64030.511.412092411087.629.43030.37510.31097252409717.31980.2510.1105527000109.38.410809.196327750120.300
The freezing point of water can be depressed to below 0° C. by adding solutes to the water. The website http://chemistry.about.com/cs/howthingswork/a/aa120703a.htm contains a list of chemicals that melt ice by lowering depressing the freezing point. This list is duplicated in Table 4. When solutes are added, the freezing point will be depressed; however, the temperature will stop falling at the freezing point until sufficient energy has been removed to freeze all of the solution so it is still easy to identify the freezing point.
TABLE 4Chemicals that Depress the Freezing Point of WaterLowestPracticalNameFormulaTempProsConsAmmonium(NH4)2SO4−7° C.FertilizerDamages concretesulfate(20° F.)CalciumCaCl2−29° C. Melts ice fasterAttracts moisture,chloride(−20° F.) thansurfaces aresodium chlorideslippery below −18° C.(0° F.)CalciumCalcium−9° C.Safest forWorks better tomagnesiumcarbonate CaCO3,(15° F.)concrete &preventacetate (CMA)magnesiumvegetationre-icing than as icecarbonateremoverMgCO3, andacetic acidCH3COOHMagnesiumMgCl2−15° C. Melts ice fasterAttracts moisturechloride (5° F.)than sodiumchloridePotassiumCH3COOK−9° C.BiodegradableCorrosiveacetate(15° F.)PotassiumKCl−7° C.FertilizerDamages concretechloride(20° F.)Sodium chlorideNaCl−9° C.Keeps sidewalksCorrosive, damages(rock salt, halite(15° F.)dryconcrete &vegetationUreaNH2CONH2−7° C.FertilizerAgricultural grade(20° F.)iscorrosive
A pleasant application of the freezing point depression is in the making of homemade ice cream. The ice cream mix is put into a metal container that is surrounded by crushed ice. Then salt is put on the ice to lower its melting point. The melting of the solution tends to lower the equilibrium temperature of the ice/water solution to the melting point of the solution. This gives a temperature gradient across the metal container into the saltwater-ice solution which is lower than 0° C. The heat transfer out of the ice cream mix allows it to freeze.
A visit to the DOW Chemical website produced FIG. 1 and Table 5 for calcium chloride. The data in table 4 assume a solution temperature of 77° F. (25°). A calcium chloride solution will allow the water to remain in the liquid state at temperatures well below the normal freezing point of water. The concentration of calcium chloride mixture will determine the new freezing point.
TABLE 5Freezing Point Depression for Calcium Chloride and Water SolutionsDowFlake 77-80%PelaDow 90-92%AnnhydrousCaCl2CaCl294-97% CaCl2ApproxApproxWeight inGal/TonGal/dry tonEquiv inEquiv inPellets EquivFreezing%Specificlb/gal(l/metric ton)(l/dry metriclb/gal orlb/gal orin lb/gal orPoint deg F.CaCl2Gravity(kg/liter)of solutionton)(kg/l) of sol(kg/l) of sol(kg/l) of sol(deg C.)01 8.31 (0.997)NANANANANA+32 (0)101.09 9.06 (1.087)221 (920)2,208 (9,200)  1.16 (0.139)1.00 (0.119)0.96 (0.114)+20 (−7)111.1 9.14 (1.097)219 (912)1,989 (8,287)  1.29 (0.155)1.10 (0.133)1.06 (0.127)+18 (−8)121.11 9.22 (1.107)217 (903)1,808 (7,528)  1.42 (0.170)1.22 (0.146)1.16 (0.140)+16 (−9)131.12 9.31 (1.117)215 (895)1,653 (6,887)  1.55 (0.186)1.33 (0.160)1.27 (0.153)+14 (−10)141.129 9.38 (1.126)213 (888)1,523 (6,334)  1.68 (0.202)1.44 (0.173)1.38 (0.166)+12 (−11)151.139 9.47 (1.136)211 (880)1,408 (5,869)  1.82 (0.218)1.56 (0.187)1.50 (0.179)+10 (−12)161.149 9.55 (1.146)209 (873)1,309 (5,454)  1.96 (0.235)1.68 (0.201)1.61 (0.193) +8 (−13)171.159 9.63 (1.156)208 (865)1,222 (5,089)  2.10 (0.252)1.80 (0.216)1.72 (0.207) +5 (−15)181.169 9.71 (1.165)206 (858)1,144 (4,769)  2.24 (0.269)1.92 (0.231)1.84 (0.221) +2 (−17)191.179 9.80 (1.175)204 (851)1,074 (4,479)  2.39 (0.286)2.05 (0.245)1.96 (0.235) −1 (−18)201.189 9.88 (1.185)202 (844)1,012 (4,219)  2.53 (0.304)2.17 (0.261)2.08 (0.250) −4 (−20)211.199 9.96 (1.195)201 (837)956 (3,985)2.68 (0.322)2.30 (0.276)2.20 (0.264) −8 (−22)221.20910.05 (1.205)199 (830)905 (3,772)2.83 (0.340)2.43 (0.291)2.33 (0.279)−12 (−24)231.21910.13 (1.215)197 (823)858 (3,578)2.99 (0.358)2.56 (0.307)2.45 (0.294)−16 (−27)241.22810.20 (1.224)196 (817)817 (3,404)3.14 (0.377)2.69 (0.323)2.58 (0.309)−20 (−29)251.2410.30 (1.236)194 (809)777 (3,236)3.30 (0.396)2.83 (0.340)2.71 (0.325)−25 (−32)261.25110.40 (1.247)192 (802)740 (3,084)3.47 (0.416)2.97 (0.356)2.85 (0.341)−31 (−35)271.26310.50 (1.259)190 (794)706 (2,942)3.63 (0.436)3.12 (0.374)2.98 (0.358)−38 (−39)281.27510.60 (1.271)189 (787)674 (2,810)3.81 (0.456)3.26 (0.391)3.12 (0.375)−46 (−43)291.28710.69 (1.283)187 (779)654 (2,688)3.97 (0.477)3.41 (0.409)3.26 (0.392)−53 (−47)291.29410.75 (1.290) 186 (775))629 (2,619 4.08 (0.490)3.50 (0.420)3.35 (0.402)−60 (−51)301.29810.79 (1.294)185 (773)618 (2,578)4.15 (0.498)3.56 (0.427)3.41 (0.409)−52 (−47)311.3110.89 (1.306)184 (766)592 (2,470)4.33 (0.519)3.71 (0.445)3.55 (0.426)−34 (−37)321.32210.99 (1.318)182 (759)569 (2,371)4.51 (0.541)3.86 (0.463)3.70 (0.444)−17 (−27)331.33411.09 (1.330)180 (752)547 (2,278)4.69 (0.563)4.02 (0.482)3.85 (0.462) −4 (−20)341.34511.18 (1.341)179 (746)526 (2,193)4.87 (0.585)4.18 (0.501)4.00 (0.480)+10 (−12)351.35711.28 (1.353)177 (739)507 (2,112)5.06 (0.607)4.34 (0.520)4.16 (0.498)+20 (−7)361.36911.38 (1.365)176 (733)488 (2,035)5.25 (0.630)4.50 (0.540)4.31 (0.517)+30 (−1)371.38111.48 (1.377)174 (726)471 (1,963)5.45 (0.653)4.67 (0.560)4.47 (0.536)+39 (+4)381.39211.57 (1.388)173 (720)455 (1,891)5.64 (0.676)4.83 (0.580)4.63 (0.555)+48 (+9)391.40411.67 (1.400)171 (714)439 (1,832)5.84 (0.700)5.00 (0.600)4.79 (0.575)+55 (+13)401.41611.77 (1.412)170 (708)425 (1,771)6.04 (0.724)5.17 (0.621)4.96 (0.594)+61 (+16)411.42811.87 (1.424)168 (702)411 (1,713)6.24 (0.748)5.35 (0.631)5.12 (0.614)+65 (+18)421.43911.96 (1.435)167 (697)398 (1,659)6.44 (0.773)5.52 (0.662)5.29 (0.634)+69 (+21)451.47412.25 (1.470)163 (680 363 (1,512)7.07 (0.848)6.06 (0.727)5.80 (0.696)+78 (+26)
The method of the invention bubbles air through a sparger into a cold-water bath to humidify (precondition) the air before sterilant vapors are introduced. The result is a continuous operation decontamination system that can operate reliably with fewer, less expensive sensors while maximizing both sterilant concentration and percent saturation
The design of the sparger that is located within the water bath should be such that it maximizes the surface to volume ratio of the air bubbles that are passing through the cold-water bath. It should also limit the velocity of the air bubbles in order to provide sufficient contact time between the air bubbles and the cold-water bath. The air stream can also be passed through a heat exchanger that will cool the air stream before it enters the sparger.
The surface to volume ratio for a spherical bubble of radius R can be calculated from the equation for the surface area of a sphere and the equation for the volume of a sphere.
            Surface      ⁢                          ⁢      Area      ⁢                          ⁢      of      ⁢                          ⁢      Sphere        =          4      ⁢      Pi      *              R        2                        Volume      ⁢                          ⁢      of      ⁢                          ⁢      a      ⁢                          ⁢      Sphere        =          4      ⁢      Pi      *                        R          3                /        3                        Surface      /      Volume        =                            4          ⁢          Pi          *                      R            2                                    4          ⁢          Pi          *                                    R              3                        /            3                              =              3        ⁢        R            
Thus, the smaller the radius, the higher is the surface to volume ratio of the of the spherical air bubble. A sintered metal sparger would generate much smaller air bubbles when compared to a sparger made by punching or drilling holes in a metal tube or plate. Mott Corporation of Farmington, Conn. has a complete product line of sintered metal spargers. The size of the sparger that is required in an application will be dependent upon the carrier air flow rates as this will determine the velocity of the air bubbles as they exit the sparger and will affect time the air stream has in contact with the cold water bath.
It may be advantageous to place a coalescing filter downstream of the water bath (refer to FIG. 17) so that any excess moister that may be entrained within the cold air stream has a surface upon which it can collect and drip back into the water bath. Sintered metal may be able to be used for this coalescing filter.
Centrifugal force can also be used to separate any excess moisture that is entrained in the air stream that is exiting the cold-water bath. The Modified Tesla turbine air pump is well suited to this purpose. A single, or a dual, modified Tesla turbine could push the carrier air flow into the sparger and withdraw it from the cold water bath, separating out excess moisture (refer to FIG. 16). As the air exits the modified Tesla turbine at a high velocity, the excess moisture is thrown to the outside of the blower by centrifugal force. As the air enters an expansion chamber and slows down, the excess moisture accumulates on the sloped, perforated air guide and drips into an accumulation chamber. The carrier airflow continues through the coalescing filter. Moisture that gathers on the coalescing filter can also drip into the accumulation chamber.